Urothelial calcium‐sensing receptor modulates micturition function via mediating detrusor activity and ameliorates bladder hyperactivity in rats

Wei Yi Wu, Shih Pin Lee, Bing Juin Chiang*, Wei Yu Lin, Chiang Ting Chien

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

摘要

The urothelium displays mechano‐ and chemosensory functions via numerous receptors and channels. The calcium‐sensing receptor (CaSR) detects extracellular calcium and modulates several physiological functions. Nonetheless, information about the expression and the role of CaSR in lower urinary tract has been absent. We aimed to determine the existence of urothelial CaSR in urinary bladder and its effect on micturition function. We utilized Western blot to confirm the expression of CaSR in bladder and used immunofluorescence to verify the location of the CaSR in the bladder urothelium via colocalization with uroplakin III A. The activation of urothelial CaSR via the CaSR agonist, AC‐265347 (AC), decreased urinary bladder smooth muscle (detrusor) ac-tivity, whereas its inhibition via the CaSR antagonist, NPS‐2143 hydrochloride (NPS), increased detrusor activity in in vitro myography experiments. Cystometry, bladder nerve activities record-ing, and bladder surface microcirculation detection were conducted to evaluate the effects of the urothelial CaSR via intravesical administrations. Intravesical AC inhibited micturition reflex, bladder afferent and efferent nerve activities, and reversed cystitis‐induced bladder hyperactivity. The urothelial CaSR demonstrated a chemosensory function, and modulated micturition reflex via regulating detrusor activity. This study provided further evidence of how the urothelial CaSR mediated micturition and implicated the urothelial CaSR as a potential pharmacotherapeutic target in the intervention of bladder disorders.

原文英語
文章編號960
期刊Pharmaceuticals
14
發行號10
DOIs
出版狀態已發佈 - 2021 10月

ASJC Scopus subject areas

  • 分子醫學
  • 藥學科學
  • 藥物發現

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